Means for reconstituting a dry biological and for controlled dispensing thereof



Feb. 20, 1968 L. HEW 3,369,708

G. MEANS FOR RECONSTITUTING A DRY BIOLOGICAL AND FOR CONTROLLEDDISPENSING THEREOF Filed Sept. 7, 1965 2 Sheets-Sheet 1 INVENTOR b4 GAQYL. HEIN m WQ E 3,369,708 NG A DRY BIOLOGICAL AND F CONTROLLED DISPENSINGTHEREOF Feb. 20, 1968 s. HEIN MEANS FOR RECONSTITUTI 2 Sheets-Sheet 2Filed Sept. 7, 1965 INVENTOIIZ GAQY L. HEIN -lfllllrlflff United StatesPatent C 3,369,708 MEANS FOR RECONSTITUTING A DRY BIOLOG- ICAL AND FORCONTROLLED DISPENSING THEREOF Gary L. Hein, Decatur, Ill., assignor toLincoln Laboratories, Inc, Decatur, 11]., a corporation of Indiana FiledSept. 7, 1965, Ser. No. 485,430 Claims. (Cl. 222-85) This inventionrelates to an improved means for reconstituting a dry, or lyophilized,biological and for thereafter effecting controlled dispensing of theliquid biological as required.

The use of lyop-hilized biologicals, such as smallpox vaccine, has theappeal of an extended shelf life prior to being reconstituted. Presenttechniques dispose the dried biological in a glass vial under a reducedgas pressure maintained by a pierceable rubber seal or stopper. Thereconstituting liquid is usually packaged in a syringe, or vial unit,having a sharp needle extending therefrom for piercing the seal on thecontainer, after which the liquid is, in the case of a syringe,expressed through the needle into the container to reconstitute thedried biological, while in the case of a vial, the reduced gas pressurein the container operates to cause the fluid to move from the vial intothe container. Thereafter, the liquid biological is either retained inthe container, from which the stopper has been removed, so as to provideaccess to the liquid by dipping or the like, or the liquid is suckedback up through the needle into the syringe unit for dispensingtherefrom as desired either through the needle or through some othertubular attachment. Both of said methods of storage of the liquidbiological have drawbacks, since an open-topped container is subject totipping and spillage therefrom, and the syringe unit requires skill incontrolling limited expressing of liquid therefrom.

Thus, one object of this invention is to provide an improved means forboth reconstituting a dried biological and for thereafter effectingsimple controlled dispensing of the liquid biological as required.

Another object of this invention is to provide an improvedselectively-controlled dispenser of liquid biologica s which obviatesthe drawbacks of existing systems and which is of simple but effectiveconstruction for achieving a more precise expressing of a very smallamount of liquid therefrom as required.

Further objects and advantages of this invention will become apparent asthe following description proceeds and the features of novelty whichcharacterize this invention will be pointed out with particularity inthe claims annexed to and forming part of this specification.

A preferred embodiment'of the invention is shown in the accompanyingdrawings, in which:

FIG. 1 illustrates an existing system for reconstituting driedbiological such as a vaccine including a container with a pierceablestopper and a syringe for introducing liquid into the container;

FIG. 2 illustrates a first form of dispenser that has been attached tothe container of liquid biological;

FIG. 3 is an enlarged fragmentary cross-section view of the dischargeend of the dispenser of FIG. 2, and showing its cooperation with a captherefor;

FIG. 4 is a vertical cross-section view of a second form of dispenserwherein the dispenser prior to its use as such, also serves as the meansfor reconstituting the dried biological;

3,369,7fi8 Patented Feb. 20, 1968 dried biological prior toreconstituting the dried biological.

Referring now to the drawings, FIG. 1 illustrates an existing system forreconstituting a dry biological and for later using a portion thereof inthe controlled dispensing of the liquid biological resulting from theprocess of reconstitution. Thus, in FIG. 1 there is shown a glass bottlegenerally indicated at 10 containing therein a preselected quantity ofdry or lyophilized biological in the form of a plurality of tablets 112.The container 10 is typically known and is normally closed by apierceable rubber stopper that is encircled by a sheet metal retainer 14which is conveniently scored along various lines 16 so that upon rupturealong such score lines the sheet metal retainer 14 may be entirelyremoved. Accompanying such a container 10 with dried biological therein,is a syringe device generally indicated at 18 and which comprises abarrel 20, a plunger 22 with a piston 23 at one end thereof located inbarrel 20, and a sharpened hollow needle 24 at the opposite end ofbarrel 20. The interior of the barrel 20 is filled with a liquidoperative to effect reconstitution of the dried biological when it hasthe pellets 12 immersed therein.

The manner of usage of this system to remove the protective sleeve 28from the needle 24, then pierce the ordinary pierceable rubber stopperon container 10 with the needle 24, and then discharge the liquidcontents 26 into the container 10, whereupon the dry biological 12 isimmersed in a bath of liquid and becomes reconstituted. Then, in orderto dispense the liquid biological in small amounts, in a controlledmanner, the container 10 is inverted so that the liquid contacts needle14, and the liquid biological is then sucked back up through needle 24to the interior of the syringe device 18. Thereafter, the liquidbiological may be dispensed either through the needle 24, or throughsome other tubular fitting that is substituted for the needle 24. Whathas thus far been described is well known in the art, and no novelty isascribed to any of these features, except insofar as some of the samestructural elements may be used to cooperate with the novel fittingshereinafter described.

Now, FIG. 2 illustrates the combination of the container It) with oneform of a novel discharge fitting at the end thereof. As earlierdescribed, the container 10 is of glass and is, therefore, a rigid,mouthed storage container that defines a restricted neck 30 and anenlarged bead 32 at the discharge end of the container 10, whichnormally surrounds and defines the mouth of the container. Thepierceable rubber stopper, which is normally provided for the container10, has been removed and discarded, and there has been attached to themouth of the container 10 a unitary dispensing device, generallyindicated at 34, for selective controlled dispensing of the liquidbiological that is within the container 10. The device 24 is molded ofpolyethylene, or rubber, or of some synthetic plastic material that isresilient enough to be manipulable in the manner as hereinafterdescribed.

The dispensing device 34 is shaped to define an annular mounting base36, whose center opening communicates with one end of the bore of anelongated dispensing tube means 38. The distal end of the tube means 38,that is remote from the base 36, terminates in a dispensing tip 40 thatis formed with a constricted orifice 42 therethrough. There is alsoprovided a flexible, bulged portion 44 intermediate the end of the tubemeans 38 and immediately adjacent the dispensing tip 49. The bulgedportion 44 has its side walls thereof thinned down as at 46, relative tothe thickness of the wall of the straight tubular portion of tube means38, that extends between the base 36 and the bulged portion 46, and theside walls of portion 44 bulge outwardly of the exterior periphery oftube 38 to define an enlarged chamber, or well, 48 that is adapted toreceive and hold a supply of liquid therein when the container isinverted, in the manner as seen in FIG. 2. The Well 48 is positionedimmediately. adjacent the dispensing tip 40 so as to locate a supply ofthe liquid to be dispensed immediately adjacent the dispensing tip.

The constricted dispensing orifice 42 is selected of such a sizerelative to the viscosity of the liquid that the liquid will not runout, under gravity forces, through orifice 42 when the container ismerely inverted, but the flexible wall portions 46 of the dispensingtube means permits of manual manipulation so as to impose controlleddispensing forces onto the liquid within the reservoir 48, so that oneis able to achieve a very accurately controlled dispensing of smallamounts of liquid biological from the tip of the dispensing tube means.Such manual manipulation may be effected, for example, by pressinginwardly on thinned walls 46 of bulged portion 44, and as illustrated inFIG. 2 a small drop 49 is being dispensed from the dispensing tip of thedevice.

The mounting base of the dispensing device 34 is appropriately molded,or shaped, to provide an annular recess 50 surrounded by skirt 51 forreceiving thereinto the enlarged bead 32 at the discharge end of thecontainer 10. It is desirable to bulge the terminal end of the skirt 51slightly inwardly at 52 to extend inwardly of the outermost portions ofbead 32 and to provide that the device snap fits onto the container. Thebase 36 is also shaped to provide thereon a sleeve type insert element54 which enters the mouth of the container and engages the inner wall ofthe restricted neck 36 to provide a good and preferably liquid-tightseal thereagainst. The portion of the base 36 which enters the mouth ofthe container is concavely recessed at 56 to provide a well, or funnel,that directs the liquid from the container 10 into the inlet end of thebore 58 of the tube means 3?.

It will be understood that the device 34 that is shown attached to thecontainer 10 in FIG. 2 is normally packaged in sterile condition in anenvelope of cellophane or the like, and after the dry biological in thecontainer 10 has been reconstituted, the envelope containing thedispensing device 34 is opened and the device is then mounted onto themouth of the container 10. In order to provide a system that inhibitsentry of air or other contaminants when the container is being storedunder refrigeration,'a closure cap 60 is provided, as best seen in FIG.3, arranged for a frictional fit onto the discharge tip 44). If desired,the closure cap 60 may be molded to provide an obturator stem 61 whichprotrudes through orifice 42 to provide an excellent seal.

In the modified form of dispensing device as shown in FIG. 4, portionssimilar to those previously described are indicated by the same numeral,primed. The dispenser 34 of FIG. 4 is intended to cooperate with andoverlie the pierceable rubber stopper 66 that is normally provided onthe container 10. Furthermore, the device of FIGS. 4 and 5 utilizes thebore space 58 within the tubular means 38' and in the well 48' of thebulged portion 44 of the dispensing tube as a storage space for thereconstituting liquid. Thus, the discharge tip 40 of the device in FIG.4 is provided thereon with a gas-tight cap or stopper 60 with obturator61', for efiecting a gastight seal at the one end of the tubularinterior of the device. At the opposite end of the bore, or canal, 58'through the tube, there is provided a hollow needle segment 62 which isheld in assembld position by gas-tight frictional engagement thereofwith the walls of the tubular part 33'. The needle 62 serves tocommunicate the interior of the storage container 10' with the entry endof the elongated dispensing tube means 38'. The outer beveled end 6% ofneedle 62 provides a piercing tip that extends below the mounting base36' of the dispenser. The mounting base 36' and its depending skirt 51'serve as annular connector means for attachment to the mouth of thecontainer 10. The outer end of the needle 62 is normally sealed by meansof a protective resilient cap 66 that is frictionally fitted over theneedle.

In usage, the entire dispensing device, with a reconstituting liquid 68therein is individually packaged, and when it is desired to reconstitutea dry biological such as at 12 in FIG. 5, the package is opened, and thesleeve, or cap, 66 is removed. Then the base 36' is snapped over theupper end of the container 10, as seen in FIG. 5, with the piercingportion 64 of the needle 62 held so that it pierces the rubber stopper66 that is normally provided on container 19. The reconstituting liquid68 is then caused to enter the container 10' to reconstitute the drybiological 12' contained therein. After reconstitution, the container 19may be inverted to effective selective discharge of liquid biologicalfrom dispensing tip 40' in the same manner as described in relation toFIG. 2.

The reconstituting liquid 68 may be caused to enter container 10 in anumber of manners. If there is a vacuum in container 10, removal of cap60 will cause the liquid 68 to be drawn into container 10' under theforce from atmospheric pressure. If there is no vacuum in container 16to draw the liquid .68 thereinto, the cap 60 is removed and manualsqueezing of the tubular means 38 progressively from the tip 4!? towardthe base 36', operates to express, or milk, the liquid into thecontainer 10'.

As to the mounting of needle 62, it will be seen that the base 36' andthe portion of canal 58' adjacent base 36' is constricted to provide arelatively thickened and less resilient mounting sleeve portion 63 aspart of the connector means that includes base 36' through which theshank of needle 62, that is located between the beveled ends of needle62, is press fit so as to rigidly position needle 62 relative to base36', and so as to maintain needle 62 in position relative to base 36'.The length of needle portion 64 which projects outwardly of base 36 isselected to be within the axial confines of skirt 51', and preferably ofa length so that only the beveled terminus of needle 62 is exposed inthe concave well 66', defined in stopper 66. This provides that almostall of the liquid in container in may enter needle 62 when the containeris inverted to the position of FIG. 2.

In the modified form of device as shown in FIGS. 6 and 7, the dispensingtube means 102 is provided as part of a stopper-shaped base 1% that isintended to fit into and connect to the mouth of a container 10, tosubstitute for the stopper that is normally provided. The base Hit} isprovided with a concave well 1 51 on the inner side. The dispensing tubemeans 102 is laterally offset from the geometric center of the base 100,and a drain tube segment 198 is rigidly mounted on base 100, andpartially extends into the canal 193 of tube means W2. A closure capEli) slidably fits onto the projecting end of drain tube 108. Thedispensing tube means 102 has a bulged portion 104 of thinned wallsadjacent the dispensing tip 106 that has a constricted bore or orificeit therethrough. A sealing cap 112 seals off the discharge tip 106. Thecanal 193 of tube means 102 and the well defined by buiged portion 104carry therein a supply of reconstituting liquid for discharge intocontainer 16, in the manner as described hercinabove in relation to thedevice of FIGS. 4 and 5.

The base 100 also carries a vent tube means 114 which extends throughthe base so that when mounted on container one end of vent tube 114 iswithin container 10 and the other end is outside of the container. Afilter 116 is carried on the outer end of vent tube 114, so that any airtaken into vent tube 114 for passage into the container 10 must firstpass through the filter 116. The filter element in filter 116 may be anyappropriate means, such as gauze or cotton. A protective sleeve, or cap,118 is provided on the extended inner end segment of vent tube 114. Thetube 114 projects much further into container 10 than does tube 108, sothat vent 114 is operable for venting even when the container isinverted.

In use, the caps 110 and 118 are first removed and the base 100 ismounted on the container, as seen in FIG. 7. Then cap 112 is removed sothat the reconstituting liquid may be caused to enter container 10 todissolve the dry biological 122, after which the combination containerand dispenser of FIG. 7 may be used in the manner as disclosed inconnection with the description of FIG. 2. The vent means 114contributes to the ease in dispensing of liquid in controlled size ofdroplets and prevents air lock from interfering with the dispensing ofbiological from the tube means 102.

While there has been shown and described a particular embodiment of thisinvention, it will be obvious to those skilled in the art that variouschanges and modifications may be made therein without departing from theinvention and, therefore, it is intended in the appended claims to coverall such changes and modifications as fall within the true spirit andscope of the invention.

What I claim as new, and desire to secure by Letters Patent of theUnited States, is:

1. A device for reconstituting a dried biological to liquid form and foreffecting selective controlled dispensing of the reconstituted liquidbiological, comprising, in combination: a storage container havingtherein a supply of biological in dried form, elongated tube meanscarrying a supply of liquid therein that is adapted to be selectivelyreleased to reconstitute the dried biological in the storage container,removable closure means at the ends of the tube means for maintainingthe supply of liquid in the tube means prior to use, connector means atone end of said tube means for attaching the elongated tube means to thestorage container, the other end of said tube means defining adispensing tip thereat with a discharge orifice therethrough, means forcausing the supply of liquid in the tube means to enter the storagecontainer when the removable closure means at said one end of the tubemeans has been removed to reconstitute the dried biological, and saidtube means providing a flexible portion therein adjacent the dispensingtip, which flexible portion is adapted to receive therein liquid fromsaid container when the container is inverted so as to locate a supplyof the reconstituted liquid biological within the tube means adjacentsaid other end when it is desired to dispense liquid therefrom, and saidflexible portion being constructed to be flexed by manual digitalpressure to effect controlled expressing of liquid biological from thedispensing tip when the removable closure means at said other end of thetube means is removed.

2. A device as set forth in claim 1 wherein said flexible portion of thetube means is bulged to form an enlarged reservoir for reconstitutingliquid that is carried in said tube means, the discharge orifice of thetube means being constricted to prevent liquid from running out throughsaid orifice under gravity forces, and the walls of said bulged portionbeing thinned relative to the remainder of the tube means to permit ofmanual manipulation thereof for achieving accurate pressurizing of theliquid in the enlarged reservoir to effect dispensing of small, preciseamounts of liquid from said dispensing tip.

3. A device as set forth in claim 1 wherein a rigid hollow drain tube isprovided extending outwardly from said one end of the tube means forcommunicating the resilient material and the connector means is formedto engage and relatively rigidly mount the hollow drain tube relative tosaid tube means, and the outwardly extending end of the drain tube beingsharpened to provide a needle-like piercing point.

5. A device as set forth in claim 1 including venting means separatefrom said tube means and carried by said connector means for enteringinto the interior of the storage container to vent the container whenthe connector means connects the tube means to the storage container.

6. A device as set forth in claim 1 wherein the means for causing thesupply of liquid in the tube means to enter the storage containerincludes the storage container with dried biological therein having agas pressure therein reduced below atmospheric pressure.

7. A device for both reconstituting a dried biological within a storagecontainer and for thereafter dispensing said reconstituted biologicalfrom said storage container through said device; said device comprising,in combination, elongated tube means carrying a supply of reconstitutingliquid therein, an aperture means at each end of said tube means, aremovable closure means for maintaining each aperture means closed priorto use of the device, connector means operatively associated with saidtube means for selectively attaching one end of the tube means to astorage container after the removable closure means at the said one endof the tube means has been removed, the aperture means at one end of thetube means affording flow of the reconstituting liquid therethrough fromthe tube means to the storage container, and the other end of the tubemeans defining a dispensing tip thereat through which liquid may beselectively expressed by manual digital pressure after the removableclosure means at the other end of the tube means has been removed.

8. In a device for controlled dispensing of liquid such as a biologicalfrom a rigid, mouthed storage container for the liquid, the improvementcomprising a body of resilient material shaped to define an elongatedtube means surrounding an elongated bore one end of which is open andadapted to have liquid move freely therethrough into and out of the boreof said tube means, the other end of said bore communicating with aconstricted discharge orifice in a discharge tip on said body at one endof the tube means which prevents liquid from running through saidorifice under gravity forces, a portion of the elongated tube meansadjacent said discharge tip defining a bulged tube portion that isflexible relative to said discharge tip and which surrounds an enlargedsection of the bore that serves as a liquid reservoir immediatelyadjacent the constricted discharge orifice, the reservoir having across-section dimension at the bulged tube portion that is greater thanany other cross-section of the bore in said tube means, and saidrelatively flexible bulged tube portion permitting of digital pressureon liquid in said reservoir adjacent the discharge orifice to effectcontrolled expressing of a precise amount of liquid from said dischargetip.

9. A device as in claim 8 wherein the body of resilient material isshaped to define an annular resilient connector integral with the tubemeans adjacent said open one end of the bore, and a hollow piercingneedle, separate from said body, is held by the resilient material ofthe body in said tube means in communication with said bore andprojecting outwardly of the said open end of the bore.

10. A device as in claim 8 wherein the bore of the tube means carries asupply of liquid pre-assembled there in, and removable closure means areprovided at the ends of the tube means for maintaining the supply ofliquid in the tube means prior to use.

References Cited UNITED STATES PATENTS Knapp 222-490 X Orson 215-11Reichel 128272 Little 21511 Ward et a1. 222-88 Rodriguez 215-11 X Little22285 Holmes 215-11 X 8 3/1961 Murrish 128272 5/1964 Yorker et al.222563 X 7/1964 Tsochatzoulos 128272 9/1964 Hansen et al. 21511 1/1965Ford 128172 4/1965 Lucht 222-490 X 8/1966 Barnby 21511 X FOREIGN PATENTS12/ 1949 France. 12/ 1949 Great Britain.

1/1955 Italy.

WALTER SOBIN, Primary Examiner.

1. A DEVICE FOR RECONSTITUTING A DRIED BIOLOGICAL TO LIQUID FORM AND FOREFFECTING SELECTIVE CONTROLLED DISPENSING OF THE RECONSTITUTED LIQUIDBIOLOGICAL, COMPRISING, IN COMBINATION: A STORAGE CONTAINER HAVINGTHEREIN A SUPPLY OF BIOLOGICAL IN DRIED FORM, ELONGATED TUBE MEANSCARRYING A SUPPLY OF LIQUID THEREIN THAT IS ADAPTED TO BE SELECTIVELYRELEASED TO RECONSTITUTE THE DRIED BIOLOGICAL IN THE STORAGE CONTAINER,REMOVABLE CLOSURE MEANS AT THE ENDS OF THE TUBE MEANS FOR MAINTAININGTHE SUPPLY OF LIQUID IN THE TUBE MEANS PRIOR TO USE, CONNECTOR MEANS ATONE END OF SAID TUBE MEANS FOR ATTACHING THE ELONGATED TUBE MEANS TO THESTORAGE CONTAINER, THE OTHER END OF SAID TUBE MEANS DEFINING ADISPENSING TIP THEREAT WITH A DISCHARGE ORIFICE THERETHROUGH, MEANS FORCAUSING THE SUPPLY OF LIQUID IN THE TUBE MEANS TO ENTER THE STORAGECONTAINER WHEN THE REMOVABLE CLOSURE MEANS AT SAID ONE END OF